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Phosphorylated insulin like growth factor

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https://www.readbyqxmd.com/read/28938423/igfbp4-is-required-for-adipogenesis-and-influences-the-distribution-of-adipose-depots
#1
David E Maridas, Victoria E DeMambro, Phuong T Le, Subburaman Mohan, Clifford J Rosen
Insulin-like Growth Factor I (IGF-I) induces adipogenesis in vitro. IGF Binding Protein 4 (IGFBP4) is highly expressed in adipocytes and osteoblasts and is inhibitory of IGFs in vitro. We previously reported that Igfbp4 null mice (Igfbp4-/-) had decreased fat proportions at 8 and 16 weeks of age. However, the mechanism leading to the reduced adiposity remains unknown. The purpose of this study was to elucidate how IGFBP4 mediates adipose tissue development in vivo. Our results showed that inguinal (iWAT) and gonadal (gWAT) white adipose tissues from Igfbp4-/- mice had decreased weights and Pparγ expression...
July 27, 2017: Endocrinology
https://www.readbyqxmd.com/read/28932186/da-negatively-regulates-igf-i-actions-implicated-in-cognitive-function-via-interaction-of-psd95-and-nnos-in-minimal-hepatic-encephalopathy
#2
Saidan Ding, Weishan Zhuge, Xuebao Wang, Jianjing Yang, Yuanshao Lin, Chengde Wang, Jiangnan Hu, Qichuan Zhuge
Insulin-like growth factor I (IGF-I) has been positively correlated with cognitive ability. Cognitive decline in minimal hepatic encephalopathy (MHE) was shown to be induced by elevated intracranial dopamine (DA). The beneficial effect of IGF-I signaling in MHE remains unknown. In this study, we found that IGF-I content was reduced in MHE rats and that IGF-I administration mitigated cognitive decline of MHE rats. A protective effect of IGF-I on the DA-induced interaction between postsynaptic density protein 95 (PSD95) and neuronal nitric oxide synthase (nNOS) was found in neurons...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28927111/luteolin-reduces-migration-of-human-glioblastoma-cell-lines-via-inhibition-of-the-p-igf-1r-pi3k-akt-mtor-signaling-pathway
#3
Qiang Wang, Handong Wang, Yue Jia, Hui Ding, Li Zhang, Hao Pan
Luteolin (3',4',5,7-tetrahydroxyflavone) is a common dietary flavonoid, which has been demonstrated to exert anticancer effects in multiple cancer models. However, the detailed mechanisms underlying the inhibitory effect of luteolin on glioblastoma cell metastasis remain poorly understood. The present study assessed the effects of luteolin in the U251MG and U87MG human glioblastoma cell lines. Luteolin treatment significantly inhibited glioblastoma cell migration, and this effect was associated with downregulated matrix metalloproteinase (MMP)-2, MMP-9 and upregulated tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28924044/nuclear-insulin-like-growth-factor-1-receptor-phosphorylates-proliferating-cell-nuclear-antigen-and-rescues-stalled-replication-forks-after-dna-damage
#4
Ahmed Waraky, Yingbo Lin, Dudi Warsito, Felix Haglund, Eiman Aleem, Olle Larsson
We have previously shown that the insulin like growth factor 1 receptor (IGF1R) translocates to the cell nucleus, where it binds to enhancer like regions and increases gene transcription. Further studies have demonstrated that nuclear IGF1R (nIGF1R) physically and functionally interacts with some nuclear proteins, i.e. the lymphoid enhancer binding factor 1 (Lef1), histone H3, and Brahma related gene 1 proteins. In the present study, we identified the proliferating cell nuclear antigen (PCNA) as a nIGF1R binding partner...
September 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28915606/proteolytic-cleavages-in-the-extracellular-domain-of-receptor-tyrosine-kinases-by-membrane-associated-serine-proteases
#5
Li-Mei Chen, Karl X Chai
The epithelial extracellular membrane-associated serine proteases matriptase, hepsin, and prostasin are proteolytic modifying enzymes of the extracellular domain (ECD) of the epidermal growth factor receptor (EGFR). Matriptase also cleaves the ECD of the vascular endothelial growth factor receptor 2 (VEGFR2) and the angiopoietin receptor Tie2. In this study we tested the hypothesis that these serine proteases may cleave the ECD of additional receptor tyrosine kinases (RTKs). We co-expressed the proteases in an epithelial cell line with Her2, Her3, Her4, insulin receptor (INSR), insulin-like growth factor I receptor (IGF-1R), the platelet-derived growth factor receptors (PDGFRs) α and β, or nerve growth factor receptor A (TrkA)...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28911149/insulin-like-growth-factor-bioactivity-stanniocalcin-2-pregnancy-associated-plasma-protein-a-and-igf-binding-protein-4-in-pleural-fluid-and-serum-from-patients-with-pulmonary-disease
#6
Ulrick Skipper Espelund, Mette Bjerre, Rikke Hjortebjerg, Torben Riis Rasmussen, Anders Lundby, Andreas Hoeflich, Birgitte Holst Folkersen, Claus Oxvig, Jan Frystyk
Context: Members of the insulin-like growth factor (IGF) system are primarily produced in the liver and secreted into the circulation, but they are also produced, recruited, and activated locally in tissues. Objective: To compare activity and concentrations of IGF system components in pleural fluid and blood. Design: Pathological pleural fluid, secondary to lung cancer or nonmalignant disease, and matching blood samples were collected from 24 patients ages 66...
September 1, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28911141/glucagon-decreases-igf-1-bioactivity-in-humans-independently-of-insulin-by-modulating-its-binding-proteins
#7
Zeinab Sarem, Christiane Bumke-Vogt, Ayman M Mahmoud, Biruhalem Assefa, Martin O Weickert, Aikatarini Adamidou, Volker Bähr, Jan Frystyk, Matthias Möhlig, Joachim Spranger, Stefanie Lieske, Andreas L Birkenfeld, Andreas F H Pfeiffer, Ayman M Arafat
Context: Depending on its lipolytic activity, glucagon plays a promising role in obesity treatment. Glucagon-induced growth hormone (GH) release can promote its effect on lipid metabolism, although the underlying mechanisms have not been well-defined. Objective: The present study highlights the glucagon effect on the GH/insulinlike growth factor 1 (IGF-1)/IGF-binding protein (IGFBP) axis in vivo and in vitro, taking into consideration insulin as a confounding factor...
September 1, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28883617/performance-of-cervical-phigfbp-1-test-alone-or-combined-with-short-cervical-length-to-predict-spontaneous-preterm-birth-in-symptomatic-women
#8
Florent Fuchs, Marie Houllier, Soizic Leparco, Anne Guyot, Marie-Victoire Senat, Hervé Fernandez
We aimed to assess the accuracy of cervical phosphorylated insulin-like growth factor binding protein-1 (phIGFBP-1) test alone or in combination with cervical length (CL), to predict preterm birth (PTB) in symptomatic women. We performed a prospective cohort study from 2012 to 2015 including singleton pregnancies with symptoms of preterm labor, intact membranes and CL < 25 mm at 24-34 weeks of gestation. Studied outcome were spontaneous delivery within 7 and 14 days of testing and spontaneous PTB at <34 and <37 weeks of gestation...
September 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28859160/igfbp2-enhances-adipogenic-differentiation-potentials-of-mesenchymal-stem-cells-from-wharton-s-jelly-of-the-umbilical-cord-via-jnk-and-akt-signaling-pathways
#9
Yuejun Wang, Yunsong Liu, Zhipeng Fan, Dayong Liu, Fu Wang, Yongsheng Zhou
Mesenchymal stem cell (MSC)-mediated tissue engineering represents a promising strategy to address adipose tissue defects. MSCs derived from Wharton's jelly of the umbilical cord (WJCMSCs) may serve as an ideal source for adipose tissue engineering due to their abundance, safety profile, and accessibility. How to activate the directed differentiation potentials of WJCMSCs is the core point for their clinical applications. A thorough investigation of mechanisms involved in WJCMSC adipogenic differentiation is necessary to support their application in adipose tissue engineering and address shortcomings...
2017: PloS One
https://www.readbyqxmd.com/read/28808415/foxo-signaling-pathways-as-therapeutic-targets-in-cancer
#10
REVIEW
Mohd Farhan, Haitao Wang, Uma Gaur, Peter J Little, Jiangping Xu, Wenhua Zheng
Many transcription factors play a key role in cellular differentiation and the delineation of cell phenotype. Transcription factors are regulated by phosphorylation, ubiquitination, acetylation/deacetylation and interactions between two or more proteins controlling multiple signaling pathways. These pathways regulate different physiological processes and pathological events, such as cancer and other diseases. The Forkhead box O (FOXO) is one subfamily of the fork head transcription factor family with important roles in cell fate decisions and this subfamily is also suggested to play a pivotal functional role as a tumor suppressor in a wide range of cancers...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28794431/macrophage-jak2-deficiency-protects-against-high-fat-diet-induced-inflammation
#11
Harsh R Desai, Tharini Sivasubramaniyam, Xavier S Revelo, Stephanie A Schroer, Cynthia T Luk, Prashanth R Rikkala, Adam H Metherel, David W Dodington, Yoo Jin Park, Min Jeong Kim, Joshua A Rapps, Rickvinder Besla, Clinton S Robbins, Kay-Uwe Wagner, Richard P Bazinet, Daniel A Winer, Minna Woo
During obesity, macrophages can infiltrate metabolic tissues, and contribute to chronic low-grade inflammation, and mediate insulin resistance and diabetes. Recent studies have elucidated the metabolic role of JAK2, a key mediator downstream of various cytokines and growth factors. Our study addresses the essential role of macrophage JAK2 in the pathogenesis to obesity-associated inflammation and insulin resistance. During high-fat diet (HFD) feeding, macrophage-specific JAK2 knockout (M-JAK2(-/-)) mice gained less body weight compared to wildtype littermate control (M-JAK2(+/+)) mice and were protected from HFD-induced systemic insulin resistance...
August 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28793874/picropodophyllin-ppp-is-a-potent-rhabdomyosarcoma-growth-inhibitor-both-in-vitro-and-in-vivo
#12
Maciej Tarnowski, Marta Tkacz, Katarzyna Zgutka, Joanna Bujak, Patrycja Kopytko, Andrzej Pawlik
BACKGROUND: Insulin-like growth factors and insulin are important factors promoting cancer growth and metastasis. The molecules act through IGF1 (IGF1R) and insulin (InsR) receptors. Rhambodmyosarcomas (RMS) overproduce IGF2 - a potent ligand for IGF1R and, at the same time, highly express IGF1 receptor. The purpose of the study was to evaluate possible application of picropodophyllin (PPP) - a potent IGF1R inhibitor. METHODS: In our study we used a number of in vitro assays showing influence of IGF1R blockage on RMS cell lines (both ARMS and ERMS) proliferation, migration, adhesion, cell cycling and signal transduction pathways...
August 9, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28753127/igf2-mrna-binding-protein-2-is-a-tumor-promoter-that-drives-cancer-proliferation-through-its-client-mrnas-igf2-and-hmga1
#13
Ning Dai, Fei Ji, Jason Wright, Liliana Minichiello, Ruslan Sadreyev, Joseph Avruch
The gene encoding the Insulin-like Growth Factor 2 mRNA binding protein 2/IMP2 is amplified and overexpressed in many human cancers, accompanied by a poorer prognosis. Mice lacking IMP2 exhibit a longer lifespan and a reduced tumor burden at old age. Herein we show in a diverse array of human cancer cells that IMP2 overexpression stimulates and IMP2 elimination diminishes proliferation by 50-80%. In addition to its known ability to promote the abundance of Insulin-like Growth Factor 2/IGF2, we find that IMP2 strongly promotes IGF action, by binding and stabilizing the mRNA encoding the DNA binding protein HMGA1, a known oncogene...
July 28, 2017: ELife
https://www.readbyqxmd.com/read/28744224/downregulated-translation-initiation-signaling-predisposes-low-birth-weight-neonatal-pigs-to-slower-rates-of-muscle-protein-synthesis
#14
Ying Chen, Sydney R McCauley, Sally E Johnson, Robert P Rhoads, Samer W El-Kadi
Low-birth-weight (LBWT) neonates experience restricted muscle growth in their perinatal life. Our aim was to investigate the mechanisms that contribute to slower skeletal muscle growth of LBWT neonatal pigs. Twenty-four 1-day old male LBWT (816 ± 55 g) and normal-birth-weight (NBWT; 1,642 ± 55 g) littermates (n = 12) were euthanized to collect blood and longissimus dorsi (LD) muscle subsamples. Plasma glucose, insulin, and insulin-like growth factor-I (IGF-I) were lower in LBWT compared with NBWT pigs. Muscle IGF-I mRNA expression were lower in LBWT than NBWT pigs...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28729397/the-igf1r-insr-inhibitor-bi-885578-selectively-inhibits-growth-of-igf2-overexpressing-colorectal-cancer-tumors-and-potentiates-the-efficacy-of-anti-vegf-therapy
#15
Michael P Sanderson, Marco H Hofmann, Pilar Garin-Chesa, Norbert Schweifer, Andreas Wernitznig, Stefan Fischer, Astrid Jeschko, Reiner Meyer, Jurgen Moll, Thomas Pecina, Heribert Arnhof, Ulrike Weyer-Czernilofsky, Stephan K Zahn, Günther R Adolf, Norbert Kraut
Clinical studies of pharmacological agents targeting the insulin like growth factor (IGF) pathway in unselected cancer patients have so far demonstrated modest efficacy outcomes, with objective responses being rare. As such, the identification of selection biomarkers for enrichment of potential responders represents a high priority for future trials of these agents. Several reports have described high IGF2 expression in a subset of colorectal cancers (CRC), with focal IGF2 amplification being responsible for some of these cases...
July 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28711909/h2o2-attenuates-igf-1r-tyrosine-phosphorylation-and-its-survival-signaling-properties-in-neuronal-cells-via-nr2b-containing-nmda-receptor
#16
Zhiwen Zeng, Dejun Wang, Uma Gaur, Liao Rifang, Haitao Wang, Wenhua Zheng
Impairment of insulin-like growth factor I (IGF-I) signaling plays an important role in the development of neurodegeneration. In the present study, we investigated the effect of H2O2 on the survival signaling of IGF-1 and its underlying mechanisms in human neuronal cells SH-SY5Y. Our results showed that IGF-1 promoted cell survival and stimulated phosphorylation of IGF-1R as well as its downstream targets like AKT and ERK1/2 in these cells. Meanwhile, these effects of IGF-1 were abolished by H2O2 at 200μM concentration which did not cause any significant toxicity to cells itself in our experiments...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28708244/mir-199a-3p-is-involved-in-estrogen-mediated-autophagy-through-the-igf-1-mtor-pathway-in-osteocyte-like-mlo-y4-cells
#17
Jiayao Fu, Lingyu Hao, Yawen Tian, Yang Liu, Yijing Gu, Junhua Wu
To date, evidence indicates that estrogen partially modulates cellular processes through microRNAs. Autophagy is a catabolic process that is regulated by multiple factors and is associated with skeletal diseases. However, whether estrogen regulates osteocyte autophagy via microRNAs is largely unknown. In this study, we observed the up-regulation of microRNA-199a-3p, a post-transcriptional regulatory factor, in osteocytic areas in ovariectomized (OVX) mice. The mature forms of miR-199a-3p and pri-miR-199a were produced in response to estrogen signaling in osteocyte-like MLO-Y4 cells...
July 14, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28706506/identification-of-brca1-as-a-potential-biomarker-for-insulin-like-growth-factor-1-receptor-targeted-therapy-in-breast-cancer
#18
Tali Cohen-Sinai, Zoya Cohen, Haim Werner, Raanan Berger
The insulin-like growth factor-1 receptor (IGF1R) emerged in recent years as a promising therapeutic target in oncology. Identification of potential biomarkers capable of predicting response to IGF1R-targeted therapy is of cardinal importance. Tumor suppressor BRCA1 has important roles in multiple pathways, including gene transcription, DNA damage repair, and control of apoptosis. Early studies have identified the IGF1R gene as a downstream target for inhibitory regulation by wild-type, but not mutant, BRCA1...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28694839/gene-expression-profiling-of-whole-blood-cells-supports-a-more-efficient-mitochondrial-respiration-in-hypoxia-challenged-gilthead-sea-bream-sparus-aurata
#19
Juan Antonio Martos-Sitcha, Azucena Bermejo-Nogales, Josep Alvar Calduch-Giner, Jaume Pérez-Sánchez
BACKGROUND: Acclimation to abiotic challenges, including decreases in O2 availability, requires physiological and anatomical phenotyping to accommodate the organism to the environmental conditions. The retention of a nucleus and functional mitochondria in mature fish red blood cells makes blood a promising tissue to analyse the transcriptome and metabolic responses of hypoxia-challenged fish in an integrative and non-invasive manner. METHODS: Juvenile gilthead sea bream (Sparus aurata) were reared at 20-21 °C under normoxic conditions (> 85% O2 saturation) followed by exposure to a gradual decrease in water O2 concentration to 3...
2017: Frontiers in Zoology
https://www.readbyqxmd.com/read/28694663/inhibition-of-n-methyl-n-nitrosourea-induced-gastric-tumorigenesis-by-liuwei-dihuang-pill-in-db-db-mice
#20
Shan Zhuang, Yong-Mei Jian, Yong-Ning Sun
AIM: To investigate the inhibitory effect of Liuwei Dihuang Pill (LDP) on gastric tumorigenesis induced by N-methyl-N-nitrosourea (MNU) in diabetic mice. METHODS: Four-week-old mice were divided into four groups: A, 12 db/m mice treated with MNU and saline, as the non-diabetic control; B, 12 db/db mice treated with MNU and saline, as the diabetic control; C, 12 db/db mice treated with MNU and metformin, as the positive control; and D, 12 db/db mice treated with MNU and LDP...
June 21, 2017: World Journal of Gastroenterology: WJG
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